Disease-associated loci are significantly over-represented among genes bound by transcription factor 7-like 2 (TCF7L2) in vivo.

Diabetologia
J ZhaoStruan F A Grant

Abstract

Transcription factor 7-like 2 (TCF7L2) has been strongly implicated in type 2 diabetes and cancer. Our goal was to identify the DNA sequences bound by this transcription factor in vivo. We applied chromatin immunoprecipitation and sequencing to globally identify and map human DNA sequences bound by TCF7L2 in the colorectal carcinoma cell line, HCT116, where it is abundantly expressed. We identified 1,095 discrete binding sites across the genome, of which a subset were within 5 kb of 548 annotated NCBI Reference Sequence (RefSeq) genes. Despite using a cancer cell line, the most significant functions represented using pathway analysis software were related to diabetes, genetic disorders and coronary artery disease. As one of the enriched categories was related to genetic disorders, we queried our results against all published genome-wide association studies (GWAS) and found a highly significant over-representation of reported loci from among the genes bound by TCF7L2 within 5 kb (p = 7.50 × 10⁻¹⁵). This observation was primarily driven by excess loci revealed from GWAS of metabolic and cardiovascular traits; however, there was no or only minor enrichment of GWAS-derived loci for cancer, and inflammatory or neurological diseases....Continue Reading

References

Jun 1, 2000·Cytogenetics and Cell Genetics·A DuvalR Hamelin
Jan 18, 2006·Nature Genetics·Struan F A GrantKari Stefansson
Jul 21, 2006·The New England Journal of Medicine·Jose C FlorezUNKNOWN Diabetes Prevention Program Research Group
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Gregory S YochumRichard H Goodman
Apr 28, 2007·Science·UNKNOWN Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical RShaun Purcell
May 4, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stéphane CauchiPhilippe Froguel
Aug 3, 2007·The Journal of Clinical Investigation·Valeriya LyssenkoLeif Groop
Feb 2, 2008·Obesity·Stéphane CauchiPhilippe Froguel
Feb 13, 2008·Molecular and Cellular Biology·Pantelis HatzisHendrik G Stunnenberg
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Wei TangLawrence Lum
Aug 13, 2008·Diabetologia·T M FraylingJ C Florez
Feb 28, 2009·Diabetologia·P OsmarkE Renström
Jun 26, 2009·Nucleic Acids Research·Geetu TutejaKlaus H Kaestner
Jul 16, 2009·Human Molecular Genetics·Ludmila Prokunina-OlssonJennifer L Hall
Jan 26, 2010·The Journal of Clinical Endocrinology and Metabolism·Ashis K MondalSteven C Elbein

❮ Previous
Next ❯

Citations

Jan 29, 2014·Diabetes Research and Clinical Practice·R C W MaJ C Chan
Sep 28, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Katrin GuskeEva Brand
Apr 11, 2014·International Journal of Endocrinology·Kevin J BasileStruan F A Grant
Jul 13, 2014·Human Molecular Genetics·Yuedan ZhouOla Hansson
Dec 4, 2014·BMJ Open Diabetes Research & Care·Matthew E JohnsonStruan F A Grant
Jun 29, 2011·Clinical and Translational Science·Maria I Vazquez-RoqueAlan R Zinsmeister
Nov 22, 2014·Nucleic Acids Research·Luke NortonSami Heikkinen
Jul 18, 2019·Diabetology & Metabolic Syndrome·Hui-Hui WuJie Wen
Jun 1, 2014·The Journal of Clinical Endocrinology and Metabolism·Matthew E JohnsonStruan F A Grant
Feb 22, 2017·ACS Synthetic Biology·Xiong XiongHuimin Zhao
Oct 7, 2021·Journal of Cellular Physiology·Laura Del Bosque-PlataClaudia Gragnoli

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Inflammation

Inflammation plays a significant role in the development of cardiovascular diseases, an understanding of these endogenous processes is critical for evaluating the risks and potential treatment strategies. Discover the latest research on cardiovascular inflammation here.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.